Early Respiratory Mechanics and Gas Exchange after Lung Transplantation: Associations with Severe Primary Graft Dysfunction

Background: Primary Graft Dysfunction (PGD) is a major cause of early morbidity and mortality following lung transplantation (LUTX), with limited early predictive markers. This study aimed to determine whether early post-operative bedside respiratory pathophysiology can predict severe PGD at 72 hours. Methods: In this prospective, single-center study, adult LUTX recipients underwent a decremental PEEP trial (14, 10, 6 cmH₂O) within 12 hours post-reperfusion. Gas exchange (venous admixture [Qs/Qt], alveolar dead space [VdALV/Vt]), partitioned respiratory mechanics (respiratory system, chest-wall, lung compliances-CplRS, CplCW, CplLUNG), and regional ventilation/perfusion (V̇/Q̇) and collapse/overdistension (via electrical impedance tomography) were assessed. Severe PGD was defined as PaO₂/FiO₂ <200 mmHg at 72 hours with bilateral infiltrates. Results: Eight (17%) out of 47 enrolled patients developed PGD. Compared to non-PGD patients, those with PGD exhibited significantly lower CplLUNG (58 vs. 80 mL/cmH₂O, p = 0.021) and CplRS (37 vs. 44 mL/cmH₂O, p = 0.038), elevated Qs/Qt (21% vs. 5%, p < 0.001), higher VdALV/Vt (15% vs. 12%, p = 0.010), and greater lung collapse (p = 0.015). Non-PGD patients had more regions with high V̇/Q̇ (p = 0.036). In PGD, increasing PEEP reduced Qs/Qt (difference -6.1%; 95%CI, -9.1, -3.1; p=0.001) and collapse (difference -19.0%; 95%CI -27.7, -10.3; p=0.002) without altering mechanics. In non-PGD, higher PEEP induced hyperinflation (difference 16.2%; 95%CI 13.6, 18.8; p<0.001), reducing CplRS (difference -2.9 mL/cmH2O; 95%CI -4.8, -1.0; p=0.008), CplCW (difference -25.3 mL/cmH2O; 95%CI -41.9, -8.7; p=0.024), and increasing VdPHYS/Vt (difference 2.9 % 95%CI 1.2, 4.6; p = 0.010,). Qs/Qt showed the highest discriminative performance (AUC 0.92, 95%CI 0.88, 0.96) in predicting PGD development. Conclusion: Severe PGD is associated with early increases in venous admixture, reduced lung compliance, increased dead space, and patterns of collapse. These findings provide the rationale for studies exploring early pathophysiology-guided ventilatory management after LUTX.